Viruses can cause injury to the host directly, in concert with the host's immune response or by modulating the immune response such that the host is more susceptible to secondary infections. Ultimately, the anti-viral immune response is responsible for the survival of the host. This interaction between the invading microbe and the immune system has been evolving over the millennia. Some virus have acquired the ability to immunosuppress the host allowing for better spread and possible persistence. One mechanism is the infection of lymphoid cells. Infection of these cell types could lead to the modulation or suppression of the antiviral immune response. Measles virus has adapted to perform these tasks. As part of this measles virus is able to immunosuppress the host by infecting lymphoid cells. The ability of the virus to infect and alter the functions of various immune cell types have been documented. For example, natural killer (NK) cell function is compromised when infected with measles virus. Similarly, infected B cells produce much less immunoglobulin when stimulated with mitogen than uninfected B cells. While the immunosuppression is substantiated, the mechanism as to how this occurs is not known. We propose to investigate the replication of measles virus in human lymphoid cells and T cell lines/clones, as well as, B cells. In addition, we will study the effects of infection on the ability of B cells and macrophages to present specific antigens to T cell lines/clones. The importance of these studies will be to determine how infection of lymphocytes by measles virus can alter functional response to antigen. Lastly, studies are proposed to define what viral gene products can modulate lymphocyte function will be performed and how this can be reversed. These studies will provide ways to inhibit virus replication and minimize infection. Thus, this investigation will contribute to our understanding of virus-cell relationships.